The 1,5-CPMTZ homologs of pentylenetetrazole (PTZ) have received only cursory attention, partly because the hydrophobic nature of some makes their administration difficult. We wanted to know if differences in seizure potency of the 1,5-CPMTZs were related to their activity or to their brain uptake. Following i.p doses (CD50 for clonus) in mice, with sesame oil as a vehicle, the brain and plasma level time course of each 1,5-CPMTZ was determined by GLC with N-P detection. The CD50s were: tetramethylenetetrazole (C4MT), 340 mg/kg (2.74 mmol/kg); PTZ, 63 mg/kg (0.46 mmol/kg); heptamethylenetetrazole (C7MT), 37 mg/kg (0.22 mmol/kg); octamethylenetetrazole (C8MT), 140 mg/kg (0.78 mmol/kg); undecamethylenetetrazole (C11MT), 150 mg/kg (0.67 mmol/kg). The peak brain level may be a better indicator of convulsant activity than the CD50 because of differences in absorption. The peak brain levels were: C4MT, 3.0 micronmol/g; PTZ, 0.33 micronmol/g; C7MT, 0.13 micronmol/g; C8MT, 0.43 micronmol/g; C11MT, 0.16 micronmol/g. We conclude that differences in convulsant activity of the 1,5-CPMTZ homologs result from differences in intrinsic activity and are not a disposition phenomenon.